The objective of this submission is to advance the applications of a recently developed stereochemically random allylic alcohol transposition and trapping process to the synthesis of medicinally relevant structures. Complex molecule synthesis remains a laborious effort, and is often a limiting factor in establishing structure activity relationships for biologically active molecules. The judicious use of stereochemically unfaithful processes that precede stereochemically defined bond formation reactions can reduce the length of synthetic sequences, allowing for faster and more economical lead optimization. New advances in this powerful protocol create many opportunities to enhance the scope of the method. This proposal pursues five new research directions in this area. The first objective is to develop new protocols for substrate-, reagent-, or catalyst-based stereoinduction in the synthesis of densely functionalized tetrahydropyrans for use in natural product and conformational probe synthesis. The second objective is to apply the method to the synthesis of medicinally relevant nitrogen-containing heterocycles. The third and fourth objectives will lead to new approaches to control the stereochemical outcomes protocols for polycyclization reactions that lead to natural products and rigid scaffolds. The final objective is to employ a stereochemistry-editing step following a fragment-coupling step as a means to facilitate convergent syntheses of complex molecules. Increased access to enantiomerically pure medicinal leads can provide important information regarding the binding conformation of ligands in their biological targets, and enantioselective synthesis is highly desirable for chiral drugs tobe approved for use.